Background: The evaluation of psychologic states is very useful in the management of inflammatory bowel disease (IBD) patients, particularly when related to disease activity (DA). Our aim was to prospectively evaluate the relationship between psychologic distress and DA. Methods: DA and psychologic distress were evaluated in 104 IBD outpatients by means of clinical criteria and the Hospital Anxiety and Depression Scale (HADS) at base line and after 6 months. Patients were grouped in unchanged, improved, and worsened DA from base line to follow-up. Results: Repeated-measures ANOVA showed a significant group-by-time interaction for HADS anxiety (F = 89.6, P = 0.0001) and depression (F = 3.67, P = 0.03) subscales. Conclusions: Over time changes in DA significantly affect psychologic distress and are closely related to corresponding increases and decreases in anxiety and depression in IBD patients. Our findings therefore suggest that the assessment of psychologic distress, particularly anxiety, should be included in the clinical management of IBD patients.